There is accumulating evidence that phosphoionositol-specific phospholipase C (PI-PLC) is regulated by a G protein in a various biological system. PI-PLC is an important enzyme in phosphoinositide metabolism leading to the generation of two second messengers, inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 can release Ca+2 from intracellular stores and DAG is an activator of protein kinase C (PKC). Xenopus oocytes have become an ideal system for the studies of signal transduction. To identify and characterize the proteins involved in signal transduction, we have isolated and characterized cDNA clones encoding Go-alpha, Gi-alpha, Gs-alpha, ADP-ribosylation factor (ARF), ras, phospholipase C, and two species of PKC from Xenopus oocytes cDNA library. Most of these cDNA clones have been fully sequenced. Comparison of the sequences of the coding regions with mammalian cDNAs shows good homology at the nucleotide and deduced amino acid level. The conserved nature of amino acid sequences between Xenopus and mammalian species suggests that the proteins involved in signal transduction are important in evolutionary history. Northern blot analysis showed that mRNA of Xenopus Go-alpha was expressed more abundantly in brain tissue. In addition, we have molecularly cloned the ARF cDNA from both human and Xenopus. The ARF is a 21 KDa GTP-binding protein that serves as the cofactor in the cholera toxin catalyzed activation of the regulatory subunit of adenylate cyclase (gs). There is also a high homology of ARF cDNAs between different species. The availability of these cDNA clones will make it possible to pursue structure function studies and the regulation of the expressions of these proteins.